DAYBREAK: A Study of Setmelanotide in Participants With S... | NCT04963231

Label	Type	Description	Intervention Names
Stage 1: Setmelanotide (Open-Label)	Experimental	Participants received once daily SC injection of setmelanotide from Day 1 to Week 16 in an open-label treatment stage (Stage 1). Participants ≥12 years of age started on setmelanotide 2.0 milligrams (mg) once daily for approximately 2 weeks, then increased to 3.0 mg once daily. Participants <12 years of age started on setmelanotide 1.0 mg once daily for approximately 1 week, then increased to 2.0 mg once daily for approximately 1 week, then increased to 3.0 mg once daily.	Drug: Setmelanotide
Stage 2: Setmelanotide (Double-Blind)	Experimental	Participants from Stage 1 who were eligible for Stage 2 received once daily SC injection of setmelanotide 3.0 mg from Week 16 to Week 40 in a double-blind treatment Stage (Stage 2).	Drug: Setmelanotide
Stage 2: Placebo (Double-Blind)	Placebo Comparator	Participants from Stage 1 who were eligible for Stage 2 received once daily SC injection of matching placebo 3.0 mg from Week 16 to Week 40 in a double-blind treatment Stage (Stage 2).	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Setmelanotide	Drug	SC injection	Stage 1: Setmelanotide (Open-Label) Stage 2: Setmelanotide (Double-Blind)

Measure	Description	Time Frame
Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1	BMI was calculated using participant's weight and height assessments, using the following formula: BMI = Kilogram (kg)/ square meter (m^2). A significant clinically meaningful response was defined as achieving a ≥5% reduction in BMI from Baseline. Data are provided for overall and according to participants with specified primary gene. Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.	Baseline to Week 16

Measure	Description	Time Frame
Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype	BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m^2. Data are provided for overall and according to participants with specified primary gene. Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.

Name	Affiliation	Role
David Meeker, MD	Rhythm Pharmaceuticals, Inc.	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
HonorHealth Bariatric Center		Scottsdale	Arizona	85258	United States
InQuest Medical Reseacrh

PubMed Identifier	Type	Citation	Retractions
36722447	Derived	Trapp CM, Censani M. Setmelanotide: a promising advancement for pediatric patients with rare forms of genetic obesity. Curr Opin Endocrinol Diabetes Obes. 2023 Apr 1;30(2):136-140. doi: 10.1097/MED.0000000000000798. Epub 2023 Feb 1.
35797460	Derived	Cuda S, Censani M. Progress in pediatric obesity: new and advanced therapies. Curr Opin Pediatr. 2022 Aug 1;34(4):407-413. doi: 10.1097/MOP.0000000000001150. Epub 2022 Jul 5.

ID	Title	Description
FG000	Stage 1: Setmelanotide (Open-Label)	Participants received once daily subcutaneous (SC) injection of setmelanotide from Day 1 to Week 16 in an open-label treatment stage (Stage 1). Participants ≥12 years of age started on setmelanotide 2.0 milligrams (mg) once daily for approximately 2 weeks, then increased to 3.0 mg once daily. Participants <12 years of age started on setmelanotide 1.0 mg once daily for approximately 1 week, then increased to 2.0 mg once daily for approximately 1 week, then increased to 3.0 mg once daily.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 27, 2022	Aug 23, 2024

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1

BMI was calculated using participant's weight and height assessments, using the following formula: BMI = Kilogram (kg)/ square meter (m^2).

A significant clinically meaningful response was defined as achieving a ≥5% reduction in BMI from Baseline.

Data are provided for overall and according to participants with specified primary gene. Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.

Participants in the Safety Analysis Set with available data were analyzed.

Posted

Count of Participants

Participants

Baseline to Week 16

ID	Title	Description
OG000	Stage 1: Setmelanotide (Open-Label)	Participants received once daily SC injection of setmelanotide from Day 1 to Week 16 in an open-label treatment stage (Stage 1). Participants ≥12 years of age started on setmelanotide 2.0 mg once daily for approximately 2 weeks, then increased to 3.0 mg once daily. Participants <12 years of age started on setmelanotide 1.0 mg once daily for approximately 1 week, then increased to 2.0 mg once daily for approximately 1 week, then increased to 3.0 mg once daily.

Units	Counts
Participants	OG000164

Title

Denominators

Categories

Overall

- ParticipantsOG000164

Title	Measurements
	OG00049

Gene: NRP1

- ParticipantsOG000

Secondary

Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype

BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m^2.

Data are provided for overall and according to participants with specified primary gene.

Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.

Participants in the Safety Analysis Set with available data were analyzed.

Posted

Mean

Standard Deviation

Kg/m^2

Baseline, Week 16

ID	Title	Description
OG000	Stage 1: Setmelanotide (Open-Label)	Participants received once daily SC injection of setmelanotide from Day 1 to Week 16 in an open-label treatment stage (Stage 1). Participants ≥12 years of age started on setmelanotide 2.0 mg once daily for approximately 2 weeks, then increased to 3.0 mg once daily. Participants <12 years of age started on setmelanotide 1.0 mg once daily for approximately 1 week, then increased to 2.0 mg once daily for approximately 1 week, then increased to 3.0 mg once daily.

Units	Counts
Participants	OG000

Secondary

Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype

BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m^2 Data are provided for overall and according to participants with specified primary gene.

Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.

Participants in the Safety Analysis Set with available data were analyzed.

Posted

Mean

Standard Deviation

Kg/m^2

Baseline, Week 16

ID	Title	Description
OG000	Stage 1: Setmelanotide (Open-Label)	Participants received once daily SC injection of setmelanotide from Day 1 to Week 16 in an open-label treatment stage (Stage 1). Participants ≥12 years of age started on setmelanotide 2.0 mg once daily for approximately 2 weeks, then increased to 3.0 mg once daily.

Units	Counts
Participants	OG000

Secondary

Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype

Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.

Participants in the Safety Analysis Set with available data were analyzed.

Posted

Mean

Standard Deviation

percent change

Baseline, Week 16

ID	Title	Description
OG000	Stage 1: Setmelanotide (Open-Label)	Participants received once daily SC injection of setmelanotide from Day 1 to Week 16 in an open-label treatment stage (Stage 1). Participants ≥12 years of age started on setmelanotide 2.0 mg once daily for approximately 2 weeks, then increased to 3.0 mg once daily. Participants <12 years of age started on setmelanotide 1.0 mg once daily for approximately 1 week, then increased to 2.0 mg once daily for approximately 1 week, then increased to 3.0 mg once daily.

Units	Counts
Participants	OG000

Secondary

Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype

Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.

Participants in the Safety Analysis Set with available data were analyzed.

Posted

Mean

Standard Deviation

percent change

Baseline, Week 16

ID	Title	Description
OG000	Stage 1: Setmelanotide (Open-Label)	Participants received once daily SC injection of setmelanotide from Day 1 to Week 16 in an open-label treatment stage (Stage 1). Participants ≥12 years of age started on setmelanotide 2.0 mg once daily for approximately 2 weeks, then increased to 3.0 mg once daily.

Units	Counts
Participants	OG000

Secondary

Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype

Data are provided for overall and according to participants with specified primary gene.

Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.

Participants in the Safety Analysis Set with available data were analyzed.

Posted

Mean

Standard Deviation

Baseline, Week 16

ID	Title	Description
OG000	Stage 1: Setmelanotide (Open-Label)	Participants received once daily SC injection of setmelanotide from Day 1 to Week 16 in an open-label treatment stage (Stage 1). Participants ≥12 years of age started on setmelanotide 2.0 mg once daily for approximately 2 weeks, then increased to 3.0 mg once daily.

Units	Counts
Participants	OG000

Secondary

Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype

Data are provided for overall and according to participants with specified primary gene.

Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.

Participants in the Safety Analysis Set with available data were analyzed.

Posted

Mean

Standard Deviation

percent change

Baseline, Week 16

ID	Title	Description
OG000	Stage 1: Setmelanotide (Open-Label)	Participants received once daily SC injection of setmelanotide from Day 1 to Week 16 in an open-label treatment stage (Stage 1). Participants ≥12 years of age started on setmelanotide 2.0 mg once daily for approximately 2 weeks, then increased to 3.0 mg once daily.

Units	Counts
Participants	OG000

Secondary

Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype

BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m^2. The BMI Z-score indicated the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched individuals). A decrease of BMI Z-score indicates a reduction in BMI from Baseline whereas an increase of BMI-Z score indicates an increase in BMI from Baseline.

Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.

Participants in the Safety Analysis Set with available data were analyzed.

Posted

Mean

Standard Deviation

z-score

Baseline, Week 16

ID	Title	Description
OG000	Stage 1: Setmelanotide (Open-Label)	Participants received once daily SC injection of setmelanotide from Day 1 to Week 16 in an open-label treatment stage (Stage 1). Participants ≥12 years of age started on setmelanotide 2.0 mg once daily for approximately 2 weeks, then increased to 3.0 mg once daily. Participants <12 years of age started on setmelanotide 1.0 mg once daily for approximately 1 week, then increased to 2.0 mg once daily for approximately 1 week, then increased to 3 mg once daily.

Units	Counts
Participants

Secondary

Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype

Daily Hunger Questionnaire for participants ≥12 years of age is self-administered questionnaire and comprises three items. For the assessment of this endpoint, maximal hunger was corresponding to the following question: In the last 24 hours, how hungry did you feel when you were the most hungry? The response was scored separately and averaged on weekly basis. Participants rated their hunger on an 11-point numeric rating scale ranging from 0 to 10 (0 = not hungry at all, and 10 = hungriest possible).

Weekly average at Week 16 was defined as average of the available score values within 7 days in Week 16.

Baseline was defined as the average of the available score values within 7 days before or on the stage 1 open-label treatment.

Results are reported by overall participant results and by specific gene cohort.

Participants in the Safety Analysis Set with available data were analyzed.

Posted

Mean

Standard Deviation

percent change

Baseline, Week 16

ID	Title	Description
OG000	Stage 1: Setmelanotide (Open-Label)	Participants received once daily SC injection of setmelanotide from Day 1 to Week 16 in an open-label treatment stage (Stage 1). Participants ≥12 years of age started on setmelanotide 2.0 mg once daily for approximately 2 weeks, then increased to 3.0 mg once daily.

Units

Secondary

Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype

Weekly average at Week 16 was defined as average of the available score values within 7 days in Week 16.

Baseline was defined as the average of the available score values within 7 days before or on the stage 1 open-label treatment.

Results are reported by overall participant results and by specific gene cohort.

Participants in the Safety Analysis Set with available data were analyzed.

Posted

Count of Participants

Participants

Baseline, Week 16

ID	Title	Description
OG000	Stage 1: Setmelanotide (Open-Label)	Participants received once daily SC injection of setmelanotide from Day 1 to Week 16 in an open-label treatment stage (Stage 1). Participants ≥12 years of age started on setmelanotide 2.0 mg once daily for approximately 2 weeks, then increased to 3.0 mg once daily.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Injection site erythema	General disorders	MedDRA 26.0	Systematic Assessment	EG00062 affected164 at risk EG0011 affected35 at risk EG0022 affected14 at risk
Injection site pain	General disorders	MedDRA 26.0	Systematic Assessment	EG00046 affected164 at risk EG0010 affected35 at risk EG0021 affected14 at risk
Injection site induration	General disorders	MedDRA 26.0	Systematic Assessment	EG00047 affected164 at risk EG0011 affected35 at risk EG0022 affected14 at risk
Injection site pruritus	General disorders	MedDRA 26.0	Systematic Assessment	EG00049 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Fatigue	General disorders	MedDRA 26.0	Systematic Assessment	EG00029 affected164 at risk EG0010 affected35 at risk EG0021 affected14 at risk
Injection site oedema	General disorders	MedDRA 26.0	Systematic Assessment	EG00020 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Injection site bruising	General disorders	MedDRA 26.0	Systematic Assessment	EG00022 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Injection site swelling	General disorders	MedDRA 26.0	Systematic Assessment	EG0006 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Injection site reaction	General disorders	MedDRA 26.0	Systematic Assessment	EG0009 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Injection site discolouration	General disorders	MedDRA 26.0	Systematic Assessment	EG00010 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Injection site warmth	General disorders	MedDRA 26.0	Systematic Assessment	EG0003 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Pain	General disorders	MedDRA 26.0	Systematic Assessment	EG0005 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Influenza like illness	General disorders	MedDRA 26.0	Systematic Assessment	EG0005 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Injection site haemorrhage	General disorders	MedDRA 26.0	Systematic Assessment	EG0003 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Pyrexia	General disorders	MedDRA 26.0	Systematic Assessment	EG0004 affected164 at risk EG0010 affected35 at risk EG0021 affected14 at risk
Injection site haematoma	General disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Peripheral swelling	General disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Thirst	General disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Asthenia	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Chills	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Crying	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Energy increased	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Inflammation	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Injection site discomfort	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Injection site nodule	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Injection site urticaria	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Malaise	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Mucosal pigmentation	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Non-cardiac chest pain	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Oedema	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Swelling face	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Temperature intolerance	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Hunger	General disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0021 affected14 at risk
Impaired healing	General disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG000130 affected164 at risk EG0017 affected35 at risk EG0021 affected14 at risk
Ephelides	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0007 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG00011 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG00010 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0004 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Nail pigmentation	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0005 affected164 at risk EG0011 affected35 at risk EG0021 affected14 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0003 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Skin hypopigmentation	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0012 affected35 at risk EG0020 affected14 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0004 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0004 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Pigmentation disorder	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0003 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0011 affected35 at risk EG0021 affected14 at risk
Hyperkeratosis	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Solar lentigo	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Acanthosis	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Blister	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Dermatitis allergic	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Hair texture abnormal	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Intertrigo	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Keratosis pilaris	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Lipodystrophy acquired	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Papule	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Seborrhoeic dermatitis	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Skin depigmentation	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Skin discolouration	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0011 affected35 at risk EG0022 affected14 at risk
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Skin striae	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Hidradenitis	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Macule	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Nail discolouration	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Photosensitivity reaction	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Nausea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG00075 affected164 at risk EG0014 affected35 at risk EG0020 affected14 at risk
Vomiting	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG00041 affected164 at risk EG0013 affected35 at risk EG0020 affected14 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG00022 affected164 at risk EG0012 affected35 at risk EG0020 affected14 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG00013 affected164 at risk EG0012 affected35 at risk EG0022 affected14 at risk
Pigmentation lip	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0009 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0007 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0006 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Constipation	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0004 affected164 at risk EG0012 affected35 at risk EG0022 affected14 at risk
Oral pigmentation	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0004 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Odynophagia	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Tongue pigmentation	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Abdominal tenderness	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Chapped lips	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Eructation	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Faeces discoloured	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Flatulence	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Gingival hyperpigmentation	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Impaired gastric emptying	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Lip swelling	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Tongue disorder	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Tooth disorder	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0010 affected35 at risk EG0021 affected14 at risk
Dental caries	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Diverticulum intestinal	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Gastritis	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Hiatus hernia	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Mouth haemorrhage	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Oesophagitis ulcerative	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Oral macule	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Melanocytic naevus	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Systematic Assessment	EG00052 affected164 at risk EG0017 affected35 at risk EG0022 affected14 at risk
Borderline ovarian tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Large intestine benign neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Headache	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG00043 affected164 at risk EG0014 affected35 at risk EG0020 affected14 at risk
Dizziness	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0008 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Disturbance in attention	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Migraine	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Somnolence	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Formication	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Sinus headache	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Dysgeusia	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Syncope	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Nasopharyngitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG00014 affected164 at risk EG0014 affected35 at risk EG0021 affected14 at risk
COVID-19	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0007 affected164 at risk EG0011 affected35 at risk EG0021 affected14 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0005 affected164 at risk EG0010 affected35 at risk EG0021 affected14 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0004 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Influenza	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0005 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Bronchitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0003 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0012 affected35 at risk EG0020 affected14 at risk
Sinusitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0003 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Urinary tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0003 affected164 at risk EG0010 affected35 at risk EG0021 affected14 at risk
Gastroenteritis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Abscess limb	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Cellulitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Conjunctivitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Eye infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Fungal infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Onychomycosis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Oral candidiasis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Otitis externa	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Parotitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Pharyngitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Pharyngitis streptococcal	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Respiratory tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Tinea pedis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Tonsillitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Ear infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0021 affected14 at risk
Respiratory tract infection viral	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0010 affected35 at risk EG0021 affected14 at risk
Vulvovaginal candidiasis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0010 affected35 at risk EG0021 affected14 at risk
Libido increased	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG00015 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Disturbance in sexual arousal	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG00011 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Insomnia	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0005 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Depression	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0004 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Libido decreased	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0003 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Nightmare	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Suicidal ideation	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Affect lability	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Anxiety	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Mental status changes	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Mood altered	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Social anxiety disorder	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Vulvovaginal discomfort	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG00010 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Spontaneous penile erection	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG0006 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Erection increased	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG0004 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Clitoral engorgement	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Dysmenorrhoea	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Menstruation delayed	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Sexual dysfunction	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Abnormal uterine bleeding	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Amenorrhoea	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Breast pain	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Erectile dysfunction	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Intermenstrual bleeding	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Penile swelling	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Semen discolouration	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Vulvovaginal burning sensation	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG00013 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0003 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0003 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0003 affected164 at risk EG0012 affected35 at risk EG0020 affected14 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Pharyngeal ulceration	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Respiratory disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Snoring	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Throat irritation	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Upper-airway cough syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0005 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0005 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0003 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0003 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Coccydynia	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Fibromyalgia	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Musculoskeletal discomfort	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Synovial cyst	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Activated partial thromboplastin time prolonged	Investigations	MedDRA 26.0	Systematic Assessment	EG0003 affected164 at risk EG0011 affected35 at risk EG0021 affected14 at risk
Prothrombin time prolonged	Investigations	MedDRA 26.0	Systematic Assessment	EG0003 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0010 affected35 at risk EG0021 affected14 at risk
International normalised ratio increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
White blood cells urine positive	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0021 affected14 at risk
Alanine aminotransferase increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Bacterial test positive	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Blood phosphorus increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Blood urine present	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Cardiac stress test abnormal	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Electrocardiogram QT prolonged	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Eosinophil count increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
High density lipoprotein decreased	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Mean cell haemoglobin concentration decreased	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Nitrite urine present	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Platelet count increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Protein urine present	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Red cell distribution width increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
White blood cells urine	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Blood creatinine increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0010 affected35 at risk EG0021 affected14 at risk
Blood sodium decreased	Investigations	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0010 affected35 at risk EG0021 affected14 at risk
Neutrophil count decreased	Investigations	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0010 affected35 at risk EG0021 affected14 at risk
Prothrombin time prolonged	Investigations	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0021 affected14 at risk
Urine leukocyte esterase positive	Investigations	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0010 affected35 at risk EG0021 affected14 at risk
White blood cell count decreased	Investigations	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0010 affected35 at risk EG0021 affected14 at risk
Influenza A virus test positive	Investigations	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Urine analysis abnormal	Investigations	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Skin abrasion	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0003 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Urinary tract procedural complication	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Tooth fracture	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0005 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Vitamin D deficiency	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Dyslipidaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Folate deficiency	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Gout	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Increased appetite	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Iron deficiency	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG0003 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Eosinophilia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Mesenteric lymphadenitis	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Urine abnormality	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Dysuria	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Pollakiuria	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Haematuria	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Seasonal allergy	Immune system disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Drug hypersensitivity	Immune system disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Hypertension	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Hypotension	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Palpitations	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Sinus bradycardia	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Dry eye	Eye disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Eye colour change	Eye disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Blepharal pigmentation	Eye disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Ear pain	Ear and labyrinth disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0011 affected35 at risk EG0020 affected14 at risk
Ocular icterus	Hepatobiliary disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected164 at risk EG0010 affected35 at risk EG0020 affected14 at risk
Dental implantation	Surgical and medical procedures	MedDRA 26.0	Systematic Assessment	EG0000 affected164 at risk EG0010 affected35 at risk EG0021 affected14 at risk

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Stage 1: Setmelanotide (Open-Label)	Participants received once daily SC injection of setmelanotide from Day 1 to Week 16 in an open-label treatment stage (Stage 1). Participants ≥12 years of age started on setmelanotide 2.0 mg once daily for approximately 2 weeks, then increased to 3.0 mg once daily. Participants <12 years of age started on setmelanotide 1.0 mg once daily for approximately 1 week, then increased to 2.0 mg once daily for approximately 1 week, then increased to 3.0 mg once daily.	164	6	164	160	164
EG001	Stage 2: Setmelanotide (Double-Blind)	Participants from Stage 1 who were eligible for Stage 2 received once daily SC injection of setmelanotide 3.0 mg from Week 16 to Week 40 in a double-blind treatment Stage (Stage 2).	35	0	35	25	35
EG002	Stage 2: Placebo (Double-Blind)	Participants from Stage 1 who were eligible for Stage 2 received once daily SC injection of matching placebo 3.0 mg from Week 16 to Week 40 in a double-blind treatment Stage (Stage 2).	14	0	14	10	14